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Biomedicines
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Gastric Cancer Research: From Basic Science to the Clinic
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Gastric Cancer Research: From Basic Science to the Clinic

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 September 2019) | Viewed by 41593

Special Issue Editor

Dr. Yoku Hayakawa

E-Mail Website
Guest Editor
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Interests: gastrointestinal cancer; gastrointestinal stem cells; stem cell niche; metaplasia; signaling pathways; tumor microenvironment; mouse models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue will focus on understanding the pathophysiology and molecular mechanisms that regulate gastric carcinogenesis and the tools that have been used in the past and are currently available for studying them both in vitro and in vivo. In particular, we will pay attention to the relevance and difference between mouse models and human pathogenesis in the gastric research field. This issue could include reviews, opinions, or short articles from experts in this research field, and cover broad topics such as important histopathological changes and/or key molecular pathways/factors during human and mouse gastric carcinogenesis, the roles of gastric stem cells and their niche during cancer development, the cellular origin of gastric cancers, the tumor microenvironment in gastric cancers, advances in cell lines and primary organoids for gastric research, epidemiological or endoscopic data analysis, and so on. We hope that the works in this issue will be helpful for solving unanswered questions in the clinic, and advancing future basic and clinical studies.

Dr. Yoku Hayakawa
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gastric cancer
  • gastric stem cells
  • metaplasia
  • tumor microenvironment
  • mouse model
  • organoid
  • signaling pathways
  • Helicobacter

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Related Special Issue

Published Papers (6 papers)

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Research

Jump to: Review

10 pages, 3320 KiB  
Communication
The Function of Lgr5+ Cells in the Gastric Antrum Does Not Require Fzd7 or Myc In Vivo
by Dustin Flanagan, Nick Barker, Matthias Ernst, Elizabeth Vincan and Toby Phesse
Biomedicines 2019, 7(3), 50; https://doi.org/10.3390/biomedicines7030050 - 8 Jul 2019
Cited by 2 | Viewed by 4722
Abstract
The extreme chemical and mechanical forces endured by the gastrointestinal tract drive a constant renewal of the epithelial lining. Stem cells of the intestine and stomach, marked by the cell surface receptor Lgr5, preserve the cellular status-quo of their respective tissues through [...] Read more.
The extreme chemical and mechanical forces endured by the gastrointestinal tract drive a constant renewal of the epithelial lining. Stem cells of the intestine and stomach, marked by the cell surface receptor Lgr5, preserve the cellular status-quo of their respective tissues through receipt and integration of multiple cues from the surrounding niche. Wnt signalling is a critical niche component for gastrointestinal stem cells and we have previously shown that the Wnt receptor, Frizzled-7 (Fzd7), is required for gastric homeostasis and the function of Lgr5+ intestinal stem cells. Additionally, we have previously shown a requirement for the Wnt target gene Myc in intestinal homeostasis, regeneration and tumourigenesis. However, it is unknown whether Fzd7 or Myc have conserved functions in gastric Lgr5+ stem cells. Here we show that gastric Lgr5+ stem cells do not require Fzd7 or Myc and are able to maintain epithelial homeostasis, highlighting key differences in the way Wnt regulates homeostasis and Lgr5+ stem cells in the stomach compared to the intestinal epithelium. Furthermore, deletion of Myc throughout the epithelium of the gastric antrum has no deleterious effects suggesting therapeutic targeting of Myc in gastric cancer patients will be well tolerated by the surrounding normal tissue. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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17 pages, 8414 KiB  
Article
Calcium Carbonate Nanoparticles Can Activate the Epithelial–Mesenchymal Transition in an Experimental Gastric Cancer Model
by Marina Senchukova, Olesya Tomchuk, Elena Shurygina, Sergey Letuta, Eskender Alidzhanov, Hike Nikiyan and Dmitry Razdobreev
Biomedicines 2019, 7(1), 21; https://doi.org/10.3390/biomedicines7010021 - 19 Mar 2019
Cited by 4 | Viewed by 6222
Abstract
Previously, we have shown the possibility of intramucosal gastric carcinoma induction by the intragastric administration of a mixture of formaldehyde and hydrogen peroxide in rats. In this study, we report a sizable increase in carcinogenic properties of the mixture when a suspension containing [...] Read more.
Previously, we have shown the possibility of intramucosal gastric carcinoma induction by the intragastric administration of a mixture of formaldehyde and hydrogen peroxide in rats. In this study, we report a sizable increase in carcinogenic properties of the mixture when a suspension containing calcium carbonate nanoparticles was added to it. This technique allowed us to reduce both the number of the carcinogen administrations from twelve to two and the time to the cancer induction from six to four months. Although the induced tumors were represented by the intramucosal carcinomas, they were characterized by the extensive invasion of individual tumor cells and their clusters into the muscle layer and serosa as well as into the omentum and blood vessels. Considering that the invasive tumor cells were positive for vimentin, Snail and TGF-β2, we concluded that their invasion was the result of the activation of epithelial–mesenchymal transition (EMT) mechanisms. Thus, taking into account the data obtained, it can be assumed that under the conditions of inflammation or carcinogenesis, the calcium carbonate nanoparticles may affect the activation of EMT mechanisms. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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Review

Jump to: Research

10 pages, 646 KiB  
Review
Gastric Cancer Stem Cells: Current Insights into the Immune Microenvironment and Therapeutic Targets
by Lingfeng Fu, Luke Bu, Tadahito Yasuda, Mayu Koiwa, Takahiko Akiyama, Tomoyuki Uchihara, Hideo Baba and Takatsugu Ishimoto
Biomedicines 2020, 8(1), 7; https://doi.org/10.3390/biomedicines8010007 - 6 Jan 2020
Cited by 30 | Viewed by 6150
Abstract
Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) are known to be involved in chemotherapy resistance and the development of metastases. Although CSCs harbor self-renewal and tumorigenic abilities, the immune microenvironment surrounding CSCs provides various factors [...] Read more.
Gastric cancer (GC) is a leading cause of cancer-related death worldwide. Cancer stem cells (CSCs) are known to be involved in chemotherapy resistance and the development of metastases. Although CSCs harbor self-renewal and tumorigenic abilities, the immune microenvironment surrounding CSCs provides various factors and supports the maintenance of CSC properties. The current review summarizes the accumulating findings regarding the relationship between the immune microenvironment and gastric CSCs (GCSCs), which will support the possibility of developing novel therapeutic strategies for targeting GCSCs. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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Graphical abstract

9 pages, 670 KiB  
Review
Role of Muscarinic Acetylcholine Signaling in Gastrointestinal Cancers
by Mitsuru Konishi, Yoku Hayakawa and Kazuhiko Koike
Biomedicines 2019, 7(3), 58; https://doi.org/10.3390/biomedicines7030058 - 10 Aug 2019
Cited by 20 | Viewed by 6139
Abstract
In the tumor microenvironment, various stromal and immune cells accumulate and interact with cancer cells to contribute to tumor progression. Among stromal players, nerves have recently been recognized as key regulators of tumor growth. More neurotransmitters, such as catecholamines and acetylcholine (ACh), are [...] Read more.
In the tumor microenvironment, various stromal and immune cells accumulate and interact with cancer cells to contribute to tumor progression. Among stromal players, nerves have recently been recognized as key regulators of tumor growth. More neurotransmitters, such as catecholamines and acetylcholine (ACh), are present in tumors, as the cells that secrete neurotransmitters accumulate by the release of neurotrophic factors from cancer cells. In this short review, we focus on the role of nerve signaling in gastrointestinal (GI) cancers. Given that muscarinic acetylcholine receptor signaling seems to be a dominant regulator of GI stem cells and cancers, we review the function and mechanism of the muscarinic ACh pathway as a regulator of GI cancer progression. Accumulating evidence suggests that ACh, which is secreted from nerves and tuft cells, stimulates GI epithelial stem cells and contributes to cancer progression via muscarinic receptors. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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15 pages, 1892 KiB  
Review
Management of Bleeding from Unresectable Gastric Cancer
by Hideaki Kawabata, Misuzu Hitomi and Shigehiro Motoi
Biomedicines 2019, 7(3), 54; https://doi.org/10.3390/biomedicines7030054 - 24 Jul 2019
Cited by 21 | Viewed by 9446
Abstract
Bleeding from unresectable gastric cancer (URGC) is not a rare complication. Two major ways in which the management of this issue differs from the management of benign lesions are the high rate of rebleeding after successful hemostasis and that not only endoscopic therapy [...] Read more.
Bleeding from unresectable gastric cancer (URGC) is not a rare complication. Two major ways in which the management of this issue differs from the management of benign lesions are the high rate of rebleeding after successful hemostasis and that not only endoscopic therapy (ET) and transcatheter arterial embolization (TAE) but palliative radiotherapy (PRT) can be applied in the clinical setting. However, there are no specific guidelines concerning the management of URGC with bleeding. We herein discuss strategies for managing bleeding from URGC. A high rate of initial hemostasis for active bleeding is expected when using various ET modalities properly. If ET fails in patients with hemostatic instability, emergent TAE is considered in order to avoid a life-threating condition due to massive bleeding. Early PRT, especially, regimens with a high biologically effective dose (BED) of ≥39 Gy should be considered not only for patients with hemostatic failure but also for those with successful hemostasis and inactive hemorrhage, as longer duration of response with few complications can be expected. Further prospective, comparative studies considering not only the hemostatic efficacy of these modalities but the patients’ quality of life are needed in order to establish treatment strategies for bleeding from URGC. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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15 pages, 1021 KiB  
Review
The Role of Wnt and R-spondin in the Stomach During Health and Disease
by Anne-Sophie Fischer and Michael Sigal
Biomedicines 2019, 7(2), 44; https://doi.org/10.3390/biomedicines7020044 - 19 Jun 2019
Cited by 23 | Viewed by 8253
Abstract
The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, [...] Read more.
The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, proliferation and differentiation. Deregulation of Wnt signaling is involved in various pathological conditions and has been linked to malignant tissue transformation in different organ systems. The study of the Wnt signaling pathway has revealed a complex regulatory network that tightly balances the quality and strength of Wnt signaling in tissues. In this context, R-spondins are secreted proteins that stabilize Wnt receptors and enhance Wnt signaling. In this review we focus on new insights into the regulatory function of Wnt and R-spondin signaling in the stomach. In addition to its function in the healthy state, we highlight the connection between Wnt signaling and infection with Helicobacter pylori (H. pylori), a pathogen that colonizes the stomach and is the main risk factor for gastric cancer. In addition to experimental data that link Wnt signaling to carcinogenesis, we discuss that Wnt signaling is affected in a substantial proportion of patients with gastric cancer, and provide examples for potential clinical implications for altered Wnt signaling in gastric cancer. Full article
(This article belongs to the Special Issue Gastric Cancer Research: From Basic Science to the Clinic)
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